There is a long history of research into body fluid biomarkers in neurodegenerative and neuroinflammatory diseases. However, only a few biomarkers in CSF are being used in clinical practice. One of the most critical factors in CSF biomarker research is the inadequate powering of studies because of the lack of sufficient samples that can be obtained in single-center studies. Therefore, collaboration between investigators is needed to establish large biobanks of well-defined samples. Standardized protocols for biobanking are a prerequisite to ensure that the statistical power gained by increasing the numbers of CSF samples is not compromised by preanalytical factors. Here, a consensus report on recommendations for CSF collection and biobanking is presented, formed by the BioMS-eu network for CSF biomarker research in multiple sclerosis. We focus on CSF collection procedures, preanalytical factors, and high-quality clinical and paraclinical information. The biobanking protocols are applicable for CSF biobanks for research targeting any neurologic disease.

Background:People with multiple sclerosis (MS) are a vulnerable group for severe COVID- 19, particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international sample of people with MS.Methods:Data from 12 data-sources in 28 countries were aggregated (sources could include patients from 1-12 countries). Demographic (age, sex), clinical (MS-phenotype, disability), and DMT (untreated, alemtuzumab, cladribine, dimethyl-fumarate, glatiramer acetate, interferon, natalizumab, ocrelizumab, rituximab, siponimod, other DMTs) covariates were queried, alongside COVID-19 severity outcomes, hospitalisation, ICU admission, requiring artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression, adjusted for age, sex, MS-phenotype, and EDSS.Results:657(28.1%) with suspected and 1,683(61.9%) with confirmed COVID-19 were analysed. Among suspected+confirmed and confirmed-only COVID-19, 20.9% and 26.9% were hospitalised, 5.4% and 7.2% were admitted to ICU, 4.1% and 5.4% required artificial ventilation, and 3.2% and 3.9% died. Older age, progressive MS-phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl-fumarate, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.56,95%CI=1.01- 2.41; aOR=2.43,95%CI=1.48-4.02) and ICU admission (aOR=2.30,95%CI=0.98-5.39;aOR=3.93,95%CI=1.56-9.89), though only rituximab was associated with higher risk of artificial ventilation (aOR=4.00,95%CI=1.54-10.39). Compared to pooled other DMTs, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.75,95%CI=1.29- 2.38; aOR=2.76,95%CI=1.87-4.07) and ICU admission (aOR=2.55,95%CI=1.49-4.36;aOR=4.32,95%CI=2.27-8.23) but only rituximab with artificial ventilation (aOR=6.15,95%CI=3.09-12.27). Compared to natalizumab, ocrelizumab and rituximab wereassociated with hospitalisation (aOR=1.86,95%CI=1.13-3.07; aOR=2.88,95%CI=1.68-4.92) and ICU admission (aOR=2.13,95%CI=0.85-5.35; aOR=3.23,95%CI=1.17-8.91), but only rituximab with ventilation (aOR=5.52,95%CI=1.71-17.84). Importantly, associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Stratification by age, MS-phenotype, and EDSS found no indications that DMT associations with COVID-19 severity reflected differential DMT allocation by underlying COVID-19 severity.Conclusions:Using the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalisation, ICU admission, and requiring artificial ventilation, and ocrelizumab with hospitalisation and ICU admission. Despite the study’s cross-sectional design, the internal and external consistency of these results with prior studies suggests rituximab/ocrelizumab use may be a risk factor for more severe COVID-19.